The capsular saccharides of bacteria have been used for many years in vaccines against capsulated bacteria. As saccharides are T-independent antigens, however, they are poorly immunogenic. Conjugation to a carrier can convert T-independent antigens into T-dependent antigens, thereby enhancing memory responses and allowing protective immunity to develop. The most effective saccharide vaccines are therefore based on glycoconjugates, and the prototype conjugate vaccine was against Haemophilus influenzae type b (‘Hib’) [e.g. see chapter 14 of ref. 78].
Another bacterium for which conjugate vaccines have been described is Streptococcus agalactiae, also known as ‘group B streptococcus’, or simply as ‘GBS’. Much of this work has been performed by Dennis Kasper and colleagues, and is described in documents such as references 1 to 9. The Kasper process for GBS saccharide conjugation typically involves reductive amination of a purified saccharide to a carrier protein such as tetanus toxoid (TT) or CRM197 [2]. The reductive amination involves an amine group on the side chain of an amino acid in the carrier and an aldehyde group in the saccharide. As GBS capsular saccharides do not include an aldehyde group in their natural form then this is generated before conjugation by periodate oxidation of a portion of the saccharides sialic acid residues, as shown in FIG. 1 [2,10].
Although conjugate vaccines prepared in this manner for each of GBS serotypes Ia, Ib, II, III, and V have been shown to be safe and immunogenic in humans [11], there remains a need for further and better ways of preparing conjugates of GBS capsular saccharides.